The project will investigate the factors regulating synthesis, secretion and metabolism of triiodothyronine (T3) and thyroxine (T4) and evaluate the relative biological significance of these two hormones. Qualitative and quantitative aspects of thyroid hormone synthesis and secretion will be investigated using TSH stimulation. Correlation of I127 content will be made before and after TSH or TRH in animals using immunoassays of T4 and T4 in pronase digests of thyroglobulin. Animal thyroids will be prelabelled at various intervals with I131 and I125. Specific T3 antibody-sepharose conjugates will be used for immunoadsorption of labelled T3 from the digest extracts. The varying affinities of T3 and T4 for the circulating serum thyroxine-binding proteins result in different metabolic clearance rates for the two hormones and differences in partition between intracellular and extracellular sites. To determine the relative contribution of T3 and T4, which will be quantitated using both immunoassay and tracer techniques. The mechanism(s) for the control of peripheral production of T3 from T4 are not known yet there is suggestive evidence that this is a specific process. The biological implications of this conversion will be investigated using hypothyroid animals given T3 and T4. Propylthiouracil will be used to inhibit T4 to T3 conversion. Because of the short half-life of T3, constant infusions and TRH will be used in rats for precise determination of the physiological role played by this hormone in suppression of TSH synthesis and/or release. BIBLIOGRAPHIC REFERENCES: Frumess, R.D. and Larsen, P.R. Correlation of serum triiodothyronine (T3) and the thyroxine (T4) with biological effects of thyroid hormone replacement in propylthiouracil-treated rats. Metabolism 24: 547-554, 1975. Frumess, R.D. and Larsen, P.R. The effect of inhibiting triiodothyronine (T3) production from thyroxine (T4) by the propylthiouracil (PTU) on the physiological activity of T4 in thyroidectamized rats. In Thyroid Hormone Metabolism. W.A. Harland and J.S. Orr, Eds., Academic Press, New York, 125-137, 1975.